{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T09:09:52Z","timestamp":1772010592262,"version":"3.50.1"},"reference-count":111,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"The National Institutes of Health","doi-asserted-by":"crossref","award":["U54MD012388-03S2"],"award-info":[{"award-number":["U54MD012388-03S2"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Early childhood caries (ECC) is the most common chronic disease of childhood, with especially high prevalence in Arizona and Hawaii where several racial and ethnic groups experience disproportionate burden. Although ECC is a polymicrobial disease,\n                      <jats:italic>Streptococcus mutans<\/jats:italic>\n                      plays a central role in its development, and evidence suggests that strain-level genetic variation influences its cariogenic potential. Understanding whether specific\n                      <jats:italic>S. mutans<\/jats:italic>\n                      lineages are associated with higher ECC risk and whether these lineages are more common in disproportionately affected groups is an important step toward identifying biological contributors to ECC outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a cross-sectional study of 408 preschool-aged children (1\u20136 years) from Arizona and Hawaii. Saliva samples were tested for\n                      <jats:italic>S. mutans<\/jats:italic>\n                      using quantitative polymerase chain reaction (qPCR), and positive samples were genotyped using a custom amplicon sequencing assay. Logistic regression was used to evaluate associations between demographic factors (race, ethnicity, age, and sex),\n                      <jats:italic>S. mutans<\/jats:italic>\n                      colonization, and ECC status. To assess whether certain\n                      <jats:italic>S. mutans<\/jats:italic>\n                      genotypes were associated with ECC risk, we calculated a K-nearest-neighbor-smoothed risk score for each genotype based on patristic distances. Genetic markers of ECC risk were identified using a pseudo-genome-wide association approach.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ECC odds increased with age and were higher among Native Hawaiian\/Pacific Islander, Asian, American Indian, and Hispanic children compared to non-Hispanic White children, although estimates for some groups were imprecise due to limited subgroups sizes.\n                      <jats:italic>S. mutans<\/jats:italic>\n                      colonization increased ECC odds by 361%, but colonization rates did not significantly differ across groups. Genotypes from Arizona and Hawaii showed no evidence of geographic clustering but ECC risk was non-randomly distributed across the phylogeny with multiple localized regions of higher risk genotypes. Native Hawaiian\/Pacific Islander children were significantly more likely to carry higher-risk strains. Genetic markers linked with ECC risk mapped to genes involved in cariogenic processes\u2014many of which were previously shown to be upregulated in caries-active plaque.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The observed correlation between\n                      <jats:italic>S. mutans<\/jats:italic>\n                      genotype and ECC risk, together with the finding that higher-risk genotypes were more prevalent among at least one disproportionately affected group, suggests that strain-level variation may contribute to population-level disparities. The identification of functional markers linked to ECC risk further supports biologically meaningful strain-specific effects and warrants further investigation. These findings highlight the value of incorporating microbial genetic diversity into ECC risk frameworks, while recognizing that fully disentangling microbial contributions will require studies that integrate social, behavioral, and dietary determinants.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.7717\/peerj.20808","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T08:26:06Z","timestamp":1772007966000},"page":"e20808","source":"Crossref","is-referenced-by-count":0,"title":["Strain-level genomic variation of\n                    <i>Streptococcus mutans<\/i>\n                    and early childhood caries in preschool children from Northern Arizona and Hawaii"],"prefix":"10.7717","volume":"14","author":[{"given":"Ryann N.","family":"Whealy","sequence":"first","affiliation":[{"name":"Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, United States of America"},{"name":"School of Informatics, Computing, and Cyber Systems, Northern Arizona University, Flagstaff, AZ, United States of America"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tara N.","family":"Furstenau","sequence":"additional","affiliation":[{"name":"School of Informatics, Computing, and Cyber Systems, Northern Arizona University, Flagstaff, AZ, United States of America"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Roberts","sequence":"additional","affiliation":[{"name":"Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, United States of America"},{"name":"School of Informatics, Computing, and Cyber Systems, Northern Arizona University, Flagstaff, AZ, United States of America"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jill Hager","family":"Cocking","sequence":"additional","affiliation":[{"name":"Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, United States of America"},{"name":"School of Informatics, Computing, and Cyber Systems, Northern Arizona University, Flagstaff, AZ, United States of America"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daryn","family":"Erickson","sequence":"additional","affiliation":[{"name":"Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, United States of America"},{"name":"School of Informatics, Computing, and Cyber Systems, Northern Arizona University, Flagstaff, AZ, United States of America"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Breezy","family":"Brock","sequence":"additional","affiliation":[{"name":"Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, United States of America"},{"name":"School of Informatics, Computing, and Cyber Systems, Northern Arizona University, Flagstaff, AZ, United States of America"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rowan","family":"McCormick","sequence":"additional","affiliation":[{"name":"Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, United States of America"},{"name":"School of Informatics, Computing, and Cyber Systems, Northern Arizona University, Flagstaff, AZ, United States of America"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Skylar","family":"Timm","sequence":"additional","affiliation":[{"name":"Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, United States of America"},{"name":"School of Informatics, Computing, and Cyber Systems, Northern Arizona University, Flagstaff, AZ, United States of America"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Misty","family":"Pacheco","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Exercise Sciences, University of Hawaii at Hilo, Hilo, HI,  United States of America"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Summer","family":"Mochida-Meek","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Exercise Sciences, University of Hawaii at Hilo, Hilo, HI,  United States of America"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viacheslav","family":"Fofanov","sequence":"additional","affiliation":[{"name":"Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, United States of America"},{"name":"School of Informatics, Computing, and Cyber Systems, Northern Arizona University, Flagstaff, AZ, United States of America"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4443","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"10.7717\/peerj.20808\/ref-1","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1128\/JCM.01410-07","article-title":"Bacteria of dental caries in primary and permanent teeth in children and young adults","volume":"46","author":"Aas","year":"2008","journal-title":"Journal of Clinical Microbiology"},{"issue":"5","key":"10.7717\/peerj.20808\/ref-2","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.GPP3-0042-2018","article-title":"Biology of oral streptococci","volume":"6","author":"Abranches","year":"2018","journal-title":"Microbiology Spectrum"},{"key":"10.7717\/peerj.20808\/ref-3","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/0003-9969(95)00111-5","article-title":"Oral colonization by more than one clonal type of mutans streptococcus in children with nursing-bottle dental caries","volume":"41","author":"Alaluusua","year":"1996","journal-title":"Archives of Oral Biology"},{"key":"10.7717\/peerj.20808\/ref-4","volume-title":"Definition of early childhood caries (ECC)","author":"American Academy\u00a0of Pediatric\u00a0Dentistry","year":"2024"},{"key":"10.7717\/peerj.20808\/ref-5","article-title":"Statement on early childhood caries","author":"American Dental\u00a0Association","year":"2021"},{"key":"10.7717\/peerj.20808\/ref-6","first-page":"377","article-title":"Influence of colonization with mutans streptococci on caries risk in Japanese preschool children: 24 month survival analysis","volume":"22","author":"Ansai","year":"2000","journal-title":"Pediatric Dentistry"},{"key":"10.7717\/peerj.20808\/ref-7","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1128\/JCM.01993-10","article-title":"Distribution of putative virulence genes in Streptococcus mutans strains does not correlate with caries experience","volume":"49","author":"Argim\u00f3n","year":"2011","journal-title":"Journal of Clinical Microbiology"},{"key":"10.7717\/peerj.20808\/ref-8","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.meegid.2013.11.003","article-title":"Comparative genomics of oral isolates of Streptococcus mutans by in silico genome subtraction does not reveal accessory DNA associated with severe early childhood caries","volume":"21","author":"Argim\u00f3n","year":"2014","journal-title":"Infection, Genetics and Evolution"},{"key":"10.7717\/peerj.20808\/ref-9","article-title":"Oral health survey Arizona preschool children","author":"Arizona Department\u00a0of Health\u00a0Services","year":"2009"},{"key":"10.7717\/peerj.20808\/ref-10","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1111\/omi.12158","article-title":"Collagen-binding proteins of Streptococcus mutans and related streptococci","volume":"32","author":"Avil\u00e9s-Reyes","year":"2017","journal-title":"Molecular Oral Microbiology"},{"key":"10.7717\/peerj.20808\/ref-11","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1111\/omi.12162","article-title":"Acid-adaptive mechanisms of Streptococcus mutans-the more we know, the more we don\u2019t","volume":"32","author":"Baker","year":"2017","journal-title":"Molecular Oral Microbiology"},{"key":"10.7717\/peerj.20808\/ref-12","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1099\/0022-1317-51-11-941","article-title":"Different bacteriocin activities of Streptococcus mutans reflect distinct phylogenetic lineages","volume":"51","author":"Balakrishnan","year":"2002","journal-title":"Journal of Medical Microbiology"},{"key":"10.7717\/peerj.20808\/ref-13","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.job.2018.11.001","article-title":"Genomic and phenotypic diversity of Streptococcus mutans","volume":"61","author":"Bedoya-Correa","year":"2019","journal-title":"Journal of Oral Biosciences"},{"key":"10.7717\/peerj.20808\/ref-14","doi-asserted-by":"publisher","first-page":"23609","DOI":"10.3402\/jom.v6.23609","article-title":"Bacterial profiles of saliva in relation to diet, lifestyle factors, and socioeconomic status","volume":"6","author":"Belstr\u00f8m","year":"2014","journal-title":"Journal of Oral Microbiology"},{"key":"10.7717\/peerj.20808\/ref-15","first-page":"1","article-title":"Surveillance for dental caries, dental sealants, tooth retention, edentulism, and enamel fluorosis\u2013United States, 1988\u20131994 and 1999\u20132002","volume":"54","author":"Beltr\u00e1n-Aguilar","year":"2005","journal-title":"Morbidity and Mortality Weekly Report. Surveillance Summaries"},{"key":"10.7717\/peerj.20808\/ref-16","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1111\/omi.12132","article-title":"Dental caries\u2014not just holes in teeth! A perspective","volume":"31","author":"Bowen","year":"2016","journal-title":"Molecular Oral Microbiology"},{"key":"10.7717\/peerj.20808\/ref-17","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1007\/s40615-019-00688-4","article-title":"Health literacy and parental oral health knowledge, beliefs, behavior, and status among parents of American Indian newborns","volume":"7","author":"Brega","year":"2020","journal-title":"Journal of Racial and Ethnic Health Disparities"},{"key":"10.7717\/peerj.20808\/ref-18","doi-asserted-by":"publisher","first-page":"650","DOI":"10.14219\/jada.archive.2009.0250","article-title":"Beyond the dmft: the human and economic cost of early childhood caries","volume":"140","author":"Casamassimo","year":"2009","journal-title":"Journal of the American Dental Association"},{"key":"10.7717\/peerj.20808\/ref-19","doi-asserted-by":"publisher","first-page":"3216","DOI":"10.1128\/iai.56.12.3216-3220.1988","article-title":"Plasmid-containing strains of Streptococcus mutans cluster within family and racial cohorts: implications for natural transmission","volume":"56","author":"Caufield","year":"1988","journal-title":"Infection and Immunity"},{"key":"10.7717\/peerj.20808\/ref-20","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1128\/JB.01183-06","article-title":"Population structure of plasmid-containing strains of Streptococcus mutans, a member of the human indigenous biota","volume":"189","author":"Caufield","year":"2007","journal-title":"Journal of Bacteriology"},{"key":"10.7717\/peerj.20808\/ref-21","first-page":"143","article-title":"Clinical outcomes for early childhood caries (ECC): the influence of salivary mutans streptococci levels","volume":"5","author":"Chase","year":"2004","journal-title":"European Journal of Paediatric Dentistry"},{"key":"10.7717\/peerj.20808\/ref-22","doi-asserted-by":"publisher","first-page":"e107","DOI":"10.1002\/imt2.107","article-title":"Ultrafast one-pass FASTQ data preprocessing, quality control, and deduplication using fastp","volume":"2","author":"Chen","year":"2023","journal-title":"Imeta"},{"key":"10.7717\/peerj.20808\/ref-23","doi-asserted-by":"publisher","DOI":"10.1145\/2939672.2939785","article-title":"XGBoost: a scalable tree boosting system","author":"Chen","year":"2016"},{"key":"10.7717\/peerj.20808\/ref-24","doi-asserted-by":"publisher","first-page":"e2318425","DOI":"10.1001\/jamanetworkopen.2023.18425","article-title":"Analysis of race and ethnicity, socioeconomic factors, and tooth decay among US children","volume":"6","author":"Choi","year":"2023","journal-title":"JAMA Network Open"},{"key":"10.7717\/peerj.20808\/ref-25","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1093\/molbev\/mss278","article-title":"Evolutionary and population genomics of the cavity causing bacteria Streptococcus mutans","volume":"30","author":"Cornejo","year":"2013","journal-title":"Molecular Biology and Evolution"},{"key":"10.7717\/peerj.20808\/ref-26","first-page":"204","article-title":"Hawaii\u2019s silent epidemic: children\u2019s caries (dental decay)","volume":"72","author":"Deguchi","year":"2013","journal-title":"Hawaii Journal of Medicine & Public Health"},{"key":"10.7717\/peerj.20808\/ref-27","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/0003-9969(84)90165-1","article-title":"A comparison of the acid\u2013base and aciduric properties of various serotypes of the bacterium Streptococcus mutans associated with dental plaque","volume":"29","author":"Denepitiya","year":"1984","journal-title":"Archives of Oral Biology"},{"key":"10.7717\/peerj.20808\/ref-28","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1038\/ng.806","article-title":"A framework for variation discovery and genotyping using next-generation DNA sequencing data","volume":"43","author":"DePristo","year":"2011","journal-title":"Nature Genetics"},{"key":"10.7717\/peerj.20808\/ref-29","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1111\/j.1365-263X.2009.01029.x","article-title":"Trends in paediatric dental caries by poverty status in the United States, 1988\u20131994 and 1999\u20132004","volume":"20","author":"Dye","year":"2010","journal-title":"International Journal of Paediatric Dentistry"},{"key":"10.7717\/peerj.20808\/ref-30","first-page":"1","article-title":"Dental caries and sealant prevalence in children and adolescents in the United States, 2011\u20132012","author":"Dye","year":"2015","journal-title":"NCHS Data Brief"},{"key":"10.7717\/peerj.20808\/ref-31","first-page":"187","article-title":"Addressing oral health disparities in settings without a research-intensive dental school: collaborative strategies","volume":"15","author":"Easa","year":"2005","journal-title":"Ethnicity and Disease"},{"key":"10.7717\/peerj.20808\/ref-32","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/j.acap.2009.09.010","article-title":"Update on disparities in oral health and access to dental care for America\u2019s children","volume":"9","author":"Edelstein","year":"2009","journal-title":"Academic Pediatrics"},{"key":"10.7717\/peerj.20808\/ref-33","first-page":"325","article-title":"Very high salivary streptococcus mutans predicts caries progression in young children","volume":"38","author":"Edelstein","year":"2016","journal-title":"Pediatric Dentistry"},{"key":"10.7717\/peerj.20808\/ref-34","doi-asserted-by":"publisher","first-page":"2605","DOI":"10.1038\/ismej.2015.72","article-title":"Meta-omics uncover temporal regulation of pathways across oral microbiome genera during in vitro sugar metabolism","volume":"9","author":"Edlund","year":"2015","journal-title":"The ISME Journal"},{"key":"10.7717\/peerj.20808\/ref-35","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.ebiom.2017.09.027","article-title":"Streptococcus mutans adhesin biotypes that match and predict individual caries development","volume":"24","author":"Esberg","year":"2017","journal-title":"EBioMedicine"},{"key":"10.7717\/peerj.20808\/ref-36","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s12903-019-0721-9","article-title":"Risk factors of early childhood caries (ECC) among children in Beijing\u2014a prospective cohort study","volume":"19","author":"Fan","year":"2019","journal-title":"BMC Oral Health"},{"key":"10.7717\/peerj.20808\/ref-37","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1111\/j.1752-7325.2012.00367.x","article-title":"An examination of racial\/ethnic disparities in children\u2019s oral health in the United States","volume":"73","author":"Fisher-Owens","year":"2013","journal-title":"Journal of Public Health Dentistry"},{"key":"10.7717\/peerj.20808\/ref-38","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1186\/s12859-018-2225-z","article-title":"Variant site strain typer (VaST): efficient strain typing using a minimal number of variant genomic sites","volume":"19","author":"Furstenau","year":"2018","journal-title":"BMC Bioinformatics"},{"key":"10.7717\/peerj.20808\/ref-39","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1128\/mmbr.61.4.393-410.1997","article-title":"Arac\/XylS family of transcriptional regulators","volume":"61","author":"Gallegos","year":"1997","journal-title":"Microbiology and Molecular Biology Reviews: MMBR"},{"key":"10.7717\/peerj.20808\/ref-40","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1177\/0022034520979926","article-title":"Oral microbiota composition predicts early childhood caries onset","volume":"100","author":"Grier","year":"2021","journal-title":"Journal of Dental Research"},{"key":"10.7717\/peerj.20808\/ref-41","doi-asserted-by":"publisher","first-page":"4121","DOI":"10.1128\/JCM.01232-10","article-title":"Bacterial 16S sequence analysis of severe caries in young permanent teeth","volume":"48","author":"Gross","year":"2010","journal-title":"Journal of Clinical Microbiology"},{"key":"10.7717\/peerj.20808\/ref-42","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.3389\/fmicb.2017.01162","article-title":"Geography, ethnicity or subsistence-specific variations in human microbiome composition and diversity","volume":"8","author":"Gupta","year":"2017","journal-title":"Frontiers in Microbiology"},{"key":"10.7717\/peerj.20808\/ref-43","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1111\/j.1399-302X.2007.00411.x","article-title":"Microbial complexes in supragingival plaque","volume":"23","author":"Haffajee","year":"2008","journal-title":"Oral Microbiology and Immunology"},{"key":"10.7717\/peerj.20808\/ref-44","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1128\/mr.44.2.331-384.1980","article-title":"Biology, immunology, and cariogenicity of Streptococcus mutans","volume":"44","author":"Hamada","year":"1980","journal-title":"Microbiological Reviews"},{"key":"10.7717\/peerj.20808\/ref-45","doi-asserted-by":"publisher","first-page":"100436","DOI":"10.1016\/j.ssmph.2019.100436","article-title":"Oral health disparities: racial, language and nativity effects","volume":"8","author":"Han","year":"2019","journal-title":"SSM\u2014Population Health"},{"key":"10.7717\/peerj.20808\/ref-46","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1111\/j.1365-2958.1995.tb02295.x","article-title":"A family of bacteriocin ABC transporters carry out proteolytic processing of their substrates concomitant with export","volume":"16","author":"Havarstein","year":"1995","journal-title":"Molecular Microbiology"},{"key":"10.7717\/peerj.20808\/ref-47","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-5153245\/v1","article-title":"Ethnicity-specific microbiome in early childhood caries: from the functional perspectives of oral biofilm","author":"Hsu","year":"2024","journal-title":"Research Square"},{"key":"10.7717\/peerj.20808\/ref-48","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1177\/1010539512438608","article-title":"Disparities in early childhood caries and its impact on oral health\u2013related quality of life of preschool children","volume":"26","author":"Krisdapong","year":"2012","journal-title":"Asia Pacific Journal of Public Health"},{"key":"10.7717\/peerj.20808\/ref-49","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1159\/000506468","article-title":"Oral lactobacilli related to caries status of children with primary dentition","volume":"54","author":"Lapirattanakul","year":"2020","journal-title":"Caries Research"},{"key":"10.7717\/peerj.20808\/ref-50","doi-asserted-by":"publisher","first-page":"4310","DOI":"10.1093\/bioinformatics\/bty539","article-title":"Pyseer: a comprehensive tool for microbial pangenome-wide association studies","volume":"34","author":"Lees","year":"2018","journal-title":"Bioinformatics"},{"key":"10.7717\/peerj.20808\/ref-51","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1111\/j.1399-302X.2007.00361.x","article-title":"Genotypic and phenotypic analysis of Streptococcus mutans from different oral cavity sites of caries-free and caries-active children","volume":"22","author":"Lembo","year":"2007","journal-title":"Oral Microbiology and Immunology"},{"key":"10.7717\/peerj.20808\/ref-52","doi-asserted-by":"publisher","first-page":"3247","DOI":"10.1099\/mic.0.2008\/023770-0","article-title":"A model of efficiency: stress tolerance by Streptococcus mutans","volume":"154","author":"Lemos","year":"2008","journal-title":"Microbiology"},{"key":"10.7717\/peerj.20808\/ref-53","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.GPP3-0051-2018","article-title":"The biology of Streptococcus mutans","volume":"7","author":"Lemos","year":"2019","journal-title":"Microbiology Spectrum"},{"key":"10.7717\/peerj.20808\/ref-54","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.1303.3997","article-title":"Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM","author":"Li","year":"2013"},{"key":"10.7717\/peerj.20808\/ref-55","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1177\/00220345950740020901","article-title":"The fidelity of initial acquisition of mutans streptococci by infants from their mothers","volume":"74","author":"Li","year":"1995","journal-title":"Journal of Dental Research"},{"key":"10.7717\/peerj.20808\/ref-56","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1177\/154405910508400905","article-title":"Mode of delivery and other maternal factors influence the acquisition of Streptococcus mutans in infants","volume":"84","author":"Li","year":"2005","journal-title":"Journal of Dental Research"},{"key":"10.7717\/peerj.20808\/ref-57","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1128\/JCM.01622-06","article-title":"Genetic profiling of the oral microbiota associated with severe early-childhood caries","volume":"45","author":"Li","year":"2007","journal-title":"Journal of Clinical Microbiology"},{"key":"10.7717\/peerj.20808\/ref-58","doi-asserted-by":"publisher","first-page":"777504","DOI":"10.3389\/fmicb.2021.777504","article-title":"F0F1-ATPase contributes to the fluoride tolerance and cariogenicity of Streptococcus mutans","volume":"12","author":"Li","year":"2021","journal-title":"Frontiers in Microbiology"},{"key":"10.7717\/peerj.20808\/ref-59","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1111\/j.1399-302x.1986.tb00322.x","article-title":"The identification of bacteria associated with periodontal disease and dental caries by enzymatic methods","volume":"1","author":"Loesche","year":"1986","journal-title":"Oral Microbiology and Immunology"},{"key":"10.7717\/peerj.20808\/ref-60","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1128\/mr.50.4.353-380.1986","article-title":"Role of Streptococcus mutans in human dental decay","volume":"50","author":"Loesche","year":"1986","journal-title":"Microbiological Reviews"},{"key":"10.7717\/peerj.20808\/ref-61","doi-asserted-by":"publisher","first-page":"1252","DOI":"10.1128\/iai.11.6.1252-1260.1975","article-title":"Association of Streptococcus mutants with human dental decay","volume":"11","author":"Loesche","year":"1975","journal-title":"Infection and Immunity"},{"key":"10.7717\/peerj.20808\/ref-62","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.1705.07874","article-title":"A unified approach to interpreting model predictions","author":"Lundberg","year":"2017"},{"key":"10.7717\/peerj.20808\/ref-63","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1111\/jphd.12563","article-title":"Racial\/ethnic disparities in preventive dental services use and dental caries among children","volume":"83","author":"Luo","year":"2023","journal-title":"Journal of Public Health Dentistry"},{"key":"10.7717\/peerj.20808\/ref-64","doi-asserted-by":"publisher","first-page":"27182","DOI":"10.3402\/jom.v7.27182","article-title":"Genotypic characterization of initial acquisition of Streptococcus mutans in American Indian children","volume":"7","author":"Lynch","year":"2015","journal-title":"Journal of Oral Microbiology"},{"key":"10.7717\/peerj.20808\/ref-65","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1186\/s12903-023-03346-8","article-title":"Is Mutans Streptococci count a risk predictor of early childhood caries? A systematic review and meta-analysis","volume":"23","author":"Manchanda","year":"2023","journal-title":"BMC Oral Health"},{"key":"10.7717\/peerj.20808\/ref-66","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1177\/08959374940080022001","article-title":"Microbial ecology of dental plaque and its significance in health and disease","volume":"8","author":"Marsh","year":"1994","journal-title":"Advances in Dental Research"},{"key":"10.7717\/peerj.20808\/ref-67","doi-asserted-by":"publisher","first-page":"e184\u201391","DOI":"10.1542\/peds.112.3.e184","article-title":"Dental caries and beverage consumption in young children","volume":"112","author":"Marshall","year":"2003","journal-title":"Pediatrics"},{"key":"10.7717\/peerj.20808\/ref-68","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.jdsr.2017.08.002","article-title":"Role of Streptococcus mutans surface proteins for biofilm formation","volume":"54","author":"Matsumoto-Nakano","year":"2018","journal-title":"The Japanese Dental Science Review"},{"key":"10.7717\/peerj.20808\/ref-69","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1177\/00220345241303880","article-title":"Streptococcus mutans and caries: a systematic review and meta-analysis","volume":"104","author":"Mazurel","year":"2025","journal-title":"Journal of Dental Research"},{"key":"10.7717\/peerj.20808\/ref-70","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1007\/s00284-017-1305-z","article-title":"Exploring the genomic diversity and cariogenic differences of Streptococcus mutans strains through pan-genome and comparative genome analysis","volume":"74","author":"Meng","year":"2017","journal-title":"Current Microbiology"},{"key":"10.7717\/peerj.20808\/ref-71","doi-asserted-by":"publisher","first-page":"2001","DOI":"10.1128\/IAI.03022-14","article-title":"The collagen binding protein Cnm contributes to oral colonization and cariogenicity of Streptococcus mutans OMZ175","volume":"83","author":"Miller","year":"2015","journal-title":"Infection and Immunity"},{"key":"10.7717\/peerj.20808\/ref-72","doi-asserted-by":"publisher","first-page":"77","DOI":"10.3290\/j.ohpd.a34997","article-title":"Early childhood caries: epidemiology, severity and sociobehavioural determinants","volume":"14","author":"Moimaz","year":"2016","journal-title":"Oral Health & Preventive Dentistry"},{"key":"10.7717\/peerj.20808\/ref-73","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1111\/omi.12254","article-title":"Streptococcus mutans serotypes and collagen-binding proteins Cnm\/Cbm in children with caries analysed by PCR","volume":"34","author":"Momeni","year":"2019","journal-title":"Molecular Oral Microbiology"},{"key":"10.7717\/peerj.20808\/ref-74","doi-asserted-by":"publisher","first-page":"2847","DOI":"10.1007\/s00784-018-2371-8","article-title":"Transmission patterns of Streptococcus mutans demonstrated by a combined rep-PCR and MLST approach","volume":"22","author":"Momeni","year":"2018","journal-title":"Clinical Oral Investigations"},{"key":"10.7717\/peerj.20808\/ref-75","doi-asserted-by":"publisher","first-page":"6943","DOI":"10.21105\/joss.06943","article-title":"DendroPy 5: a mature Python library for phylogenetic computing","volume":"9","author":"Moreno","year":"2024","journal-title":"Journal of Open Source Software"},{"key":"10.7717\/peerj.20808\/ref-76","doi-asserted-by":"publisher","first-page":"2616","DOI":"10.1128\/JCM.02343-06","article-title":"Streptococcus mutans clonal variation revealed by multilocus sequence typing","volume":"45","author":"Nakano","year":"2007","journal-title":"Journal of Clinical Microbiology"},{"key":"10.7717\/peerj.20808\/ref-77","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1101\/gr.084616.108","article-title":"Global diversity in the human salivary microbiome","volume":"19","author":"Nasidze","year":"2009","journal-title":"Genome Research"},{"key":"10.7717\/peerj.20808\/ref-78","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1093\/molbev\/msu300","article-title":"IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies","volume":"32","author":"Nguyen","year":"2015","journal-title":"Molecular Biology and Evolution"},{"issue":"Suppl 1","key":"10.7717\/peerj.20808\/ref-79","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1111\/j.1752-7325.2000.tb04069.x","article-title":"Prevalence and severity of dental caries among American Indians and Alaska Natives","volume":"60","author":"Niendorff","year":"2000","journal-title":"Journal of Public Health Dentistry"},{"key":"10.7717\/peerj.20808\/ref-80","article-title":"National call to action to promote oral health","author":"Office of\u00a0the Surgeon General\u00a0(US)","year":"2003"},{"key":"10.7717\/peerj.20808\/ref-81","doi-asserted-by":"publisher","first-page":"D733","DOI":"10.1093\/nar\/gkv1189","article-title":"Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation","volume":"44","author":"O\u2019Leary","year":"2016","journal-title":"Nucleic Acids Research"},{"key":"10.7717\/peerj.20808\/ref-82","doi-asserted-by":"publisher","first-page":"3691","DOI":"10.1093\/bioinformatics\/btv421","article-title":"Roary: rapid large-scale prokaryote pan genome analysis","volume":"31","author":"Page","year":"2015","journal-title":"Bioinformatics"},{"key":"10.7717\/peerj.20808\/ref-83","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1111\/jphd.12470","article-title":"Racial\/ethnic inequality in the association of allostatic load and dental caries in children","volume":"82","author":"Park","year":"2022","journal-title":"Journal of Public Health Dentistry"},{"key":"10.7717\/peerj.20808\/ref-84","first-page":"2825","article-title":"Scikit-learn: machine Learning in Python","volume":"12","author":"Pedregosa","year":"2011","journal-title":"Journal of Machine Learning Research"},{"key":"10.7717\/peerj.20808\/ref-85","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1111\/j.1752-7325.2012.00331.x","article-title":"Prevalence and severity of dental caries among American Indian and Alaska Native preschool children","volume":"72","author":"Phipps","year":"2012","journal-title":"Journal of Public Health Dentistry"},{"key":"10.7717\/peerj.20808\/ref-86","doi-asserted-by":"publisher","first-page":"14788","DOI":"10.1038\/s41598-020-71422-y","article-title":"Ethnic variation of oral microbiota in children","volume":"10","author":"Premaraj","year":"2020","journal-title":"Scientific Reports"},{"key":"10.7717\/peerj.20808\/ref-87","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1128\/AAC.00919-15","article-title":"Molecule targeting glucosyltransferase inhibits Streptococcus mutans biofilm formation and virulence","volume":"60","author":"Ren","year":"2016","journal-title":"Antimicrobial Agents and Chemotherapy"},{"key":"10.7717\/peerj.20808\/ref-88","doi-asserted-by":"publisher","first-page":"e000074","DOI":"10.1099\/mgen.0.000074","article-title":"NASP: an accurate, rapid method for the identification of SNPs in WGS datasets that supports flexible input and output formats","volume":"2","author":"Sahl","year":"2016","journal-title":"Microbial Genomics"},{"key":"10.7717\/peerj.20808\/ref-89","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1186\/s13073-015-0176-9","article-title":"Phylogenetically typing bacterial strains from partial SNP genotypes observed from direct sequencing of clinical specimen metagenomic data","volume":"7","author":"Sahl","year":"2015","journal-title":"Genome Medicine"},{"key":"10.7717\/peerj.20808\/ref-90","doi-asserted-by":"publisher","first-page":"2068","DOI":"10.1093\/bioinformatics\/btu153","article-title":"Prokka: rapid prokaryotic genome annotation","volume":"30","author":"Seemann","year":"2014","journal-title":"Bioinformatics"},{"key":"10.7717\/peerj.20808\/ref-91","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1111\/j.1600-051x.1998.tb02419.x","article-title":"Microbial complexes in subgingival plaque","volume":"25","author":"Socransky","year":"1998","journal-title":"Journal of Clinical Periodontology"},{"key":"10.7717\/peerj.20808\/ref-92","doi-asserted-by":"publisher","first-page":"3464","DOI":"10.1128\/JB.00119-10","article-title":"Three paralogous LysR-type transcriptional regulators control sulfur amino acid supply in Streptococcus mutans","volume":"192","author":"Sperandio","year":"2010","journal-title":"Journal of Bacteriology"},{"key":"10.7717\/peerj.20808\/ref-93","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1093\/bioinformatics\/btq228","article-title":"DendroPy: a Python library for phylogenetic computing","volume":"26","author":"Sukumaran","year":"2010","journal-title":"Bioinformatics"},{"key":"10.7717\/peerj.20808\/ref-94","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1177\/0022034510379602","article-title":"The role of bacteria in the caries process: ecological perspectives","volume":"90","author":"Takahashi","year":"2011","journal-title":"Journal of Dental Research"},{"key":"10.7717\/peerj.20808\/ref-95","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1128\/JCM.02427-10","article-title":"Cultivable anaerobic microbiota of severe early childhood caries","volume":"49","author":"Tanner","year":"2011","journal-title":"Journal of Clinical Microbiology"},{"key":"10.7717\/peerj.20808\/ref-96","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.chom.2015.08.005","article-title":"Prediction of early childhood caries via spatial-temporal variations of oral microbiota","volume":"18","author":"Teng","year":"2015","journal-title":"Cell Host & Microbe"},{"key":"10.7717\/peerj.20808\/ref-97","first-page":"176","article-title":"Risk factors for early childhood caries: an umbrella review","volume":"43","author":"Thang\u00a0Le","year":"2021","journal-title":"Pediatric Dentistry"},{"key":"10.7717\/peerj.20808\/ref-98","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1186\/s12903-017-0406-1","article-title":"Genotypic diversity and phenotypic traits of Streptococcus mutans isolates and their relation to severity of early childhood caries","volume":"17","author":"Valdez","year":"2017","journal-title":"BMC Oral Health"},{"issue":"Suppl 1","key":"10.7717\/peerj.20808\/ref-99","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.1186\/1472-6831-6-S1-S3","article-title":"Disparities in early childhood caries","volume":"6","author":"Vargas","year":"2006","journal-title":"BMC Oral Health"},{"key":"10.7717\/peerj.20808\/ref-100","article-title":"Emergency department use for dental conditions continues to increase","author":"Wall","year":"2015","journal-title":"Health Policy Institute Research Brief"},{"key":"10.7717\/peerj.20808\/ref-101","doi-asserted-by":"publisher","DOI":"10.1101\/2024.10.07.617037","article-title":"Diversity and characteristics of the oral microbiome influenced by race and ethnicity","author":"Wang","year":"2024","journal-title":"BioRxiv"},{"key":"10.7717\/peerj.20808\/ref-102","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1111\/j.1752-7325.2012.00372.x","article-title":"Dental caries in a cohort of very young American Indian children","volume":"72","author":"Warren","year":"2012","journal-title":"Journal of Public Health Dentistry"},{"key":"10.7717\/peerj.20808\/ref-103","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1111\/j.1600-0528.2008.00447.x","article-title":"A longitudinal study of dental caries risk among very young low SES children","volume":"37","author":"Warren","year":"2009","journal-title":"Community Dentistry and Oral Epidemiology"},{"key":"10.7717\/peerj.20808\/ref-104","doi-asserted-by":"publisher","DOI":"10.1101\/2025.01.30.635340","article-title":"Biological drivers of early childhood caries in preschool children of Northern Arizona and Hawaii","author":"Whealy","year":"2025","journal-title":"BioRxiv"},{"key":"10.7717\/peerj.20808\/ref-105","doi-asserted-by":"publisher","first-page":"19943","DOI":"10.1038\/s41598-019-56486-9","article-title":"Diversity of SpaP in genetic and salivary agglutinin mediated adherence among Streptococcus mutans strains","volume":"9","author":"Yang","year":"2019","journal-title":"Scientific Reports"},{"key":"10.7717\/peerj.20808\/ref-106","doi-asserted-by":"publisher","DOI":"10.1128\/mSystems.00639-19","article-title":"Racial differences in the oral microbiome: data from low-income populations of African Ancestry and European Ancestry","volume":"4","author":"Yang","year":"2019","journal-title":"MSystems"},{"key":"10.7717\/peerj.20808\/ref-107","doi-asserted-by":"publisher","first-page":"4438","DOI":"10.1128\/JCM.41.9.4438-4441.2003","article-title":"Development of a 5\u2019 nuclease-based real-time PCR assay for quantitative detection of cariogenic dental pathogens Streptococcus mutans and Streptococcus sobrinus","volume":"41","author":"Yoshida","year":"2003","journal-title":"Journal of Clinical Microbiology"},{"key":"10.7717\/peerj.20808\/ref-108","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1111\/j.1399-302X.2008.00495.x","article-title":"Comparative whole-genome analysis of Streptococcus mutans isolates within and among individuals of different caries status","volume":"24","author":"Zhang","year":"2009","journal-title":"Oral Microbiology and Immunology"},{"key":"10.7717\/peerj.20808\/ref-109","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/s41368-021-00137-1","article-title":"Molecular mechanisms of inhibiting glucosyltransferases for biofilm formation in Streptococcus mutans","volume":"13","author":"Zhang","year":"2021","journal-title":"International Journal of Oral Science"},{"issue":"Suppl 2","key":"10.7717\/peerj.20808\/ref-110","doi-asserted-by":"publisher","first-page":"100945","DOI":"10.1016\/j.identj.2025.100945","article-title":"Managing early childhood caries in asia-pacific region","volume":"75","author":"Zheng","year":"2025","journal-title":"International Dental Journal"},{"key":"10.7717\/peerj.20808\/ref-111","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1101\/gr.232397.117","article-title":"GrapeTree: visualization of core genomic relationships among 100,000 bacterial pathogens","volume":"28","author":"Zhou","year":"2018","journal-title":"Genome Research"}],"container-title":["PeerJ"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/peerj.com\/articles\/20808.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/20808.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/20808.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/20808.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T08:26:12Z","timestamp":1772007972000},"score":1,"resource":{"primary":{"URL":"https:\/\/peerj.com\/articles\/20808"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,25]]},"references-count":111,"alternative-id":["10.7717\/peerj.20808"],"URL":"https:\/\/doi.org\/10.7717\/peerj.20808","archive":["CLOCKSS","LOCKSS","Portico"],"relation":{},"ISSN":["2167-8359"],"issn-type":[{"value":"2167-8359","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,25]]},"article-number":"e20808"}}